Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-01-11
1997-08-26
Criares, Theodore J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31415
Patent
active
056611722
DESCRIPTION:
BRIEF SUMMARY
This application is filed under 35 U.S.C. 371 of PCT/FR94/00841, filed 07 Jul. 1994, which claims priority of application 93/08497 filed in France 09 Jul. 1993.
The present invention relates to the use of efaroxan and derivatives for the treatment of Alzheimer-like senile dementia, pre-Alzheimer's syndrome, progressive supranuclear palsy and other neurodegenerative diseases.
Alzheimer's disease is a progressive neurodegenerative disease particularly, but not exclusively, affecting the central cholinergic system (Meynert's nucleus basalis) manifested by a loss of cognitive faculties, a loss of intellectual capacities, and behavioral and personality disorders.
There is currently no satisfactory treatment either for treating the symptoms or for slowing its advancement. Diagnosis of the disease is difficult, and one can never be certain about diagnosing Alzheimer's disease per se. It is in particular the anatomohistological analysis performed post-mortem by, inter alia, the revelation of extraneuronal senile plaques and intraneuronal neurofibrillar networks which makes it possible to diagnose Alzheimer's disease unambiguously. A loss of cellular bodies and a depletion of neurotransmitters, in particular acetylcholine, are also associated therewith. In the absence of this histological and biochemical proof, the clinical characteristics lead to the diagnosis of a pre-Alzheimer-like neurodegenerative disease.
"Progressive Supranuclear Palsy" (PSP) is a non-hereditary evolutive neurodegenerative disease which appears late and involves perturbations of several neurotransmitters. PSP is characterized by dementia with postural instability, rigidity, associated bradykinesia, accompanied by supranuclear ophthalmoplegia. This disease appears in about 4% of patients suffering from Parkinsonism. There is currently no treatment for this disease. Palliative or symptomatological therapies do not have a satisfactory effect.
It is known that efaroxan, 2-(2-ethyl-2,3-dihydrobenzofuranyl)-2-imidazoline, possesses antagonist properties with respect to .alpha..sub.2 -adrenergic receptors. This compound is described in patent application GB-2,102,422 along with its therapeutic application as an anti-depressant and antimigraine medicinal product.
This compound and derivatives thereof are also described in patent application WO 92/05171 in which the action of the levorotatory enantiomer for treating diabetes and the action as a potassium channel blocking agent are demonstrated.
The present invention relates to the use of efaroxan and derivatives thereof for the preparation of a medicinal product intended for the treatment of Alzheimer-like senile dementia, pre-Alzheimer's syndrome, progressive supranuclear palsy and other neurodegenerative diseases.
The expression efaroxan and derivatives thereof is understood to mean the compound of formula I ##STR1## in which R.sub.1 represents a hydrogen atom or a linear or branched C.sub.1 -C.sub.6 alkyl radical, group, and chloro or bromo group, and or the optically active isomers thereof.
Advantageously, R.sub.2 and R.sub.3 represent a hydrogen atom and R.sub.1 represents an ethyl, n-propyl or i-propyl group.
The compound of general formula I is preferably chosen from the following compounds:
PHARMACOLOGICAL STUDY
A study on the activity of efaroxan on rat memory functions was performed in accordance with the described conditions (P. CHOPIN and M. BRILEY, Psychopharmacology 106, 26 (1992)).
When administered before the first passive avoidance behavior training session, scopolamine, a central antagonist, induces a dose-dependent amnesia which may be measured 48 hours later during a second session.
The administration of efaroxan, 30 minutes before the second session, decreases the amnesia induced by scopolamine, thus showing an increase in nmemonic activity by stimulation of the memory functions.
The table below shows the effect of efaroxan in the presence of scopolamine, in a dose-dependent manner, in increasing the time required for the rat to pass from a lit compartment to a dark compartmen
REFERENCES:
patent: 4855385 (1989-08-01), Kester et al.
Briley Michael
Colpaert Francis
Imbert Thierry
Criares Theodore J.
Pierre Fabre Medicament
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